MUTATIONAL ANALYSIS OF THE CD6 LIGAND-BINDING DOMAIN

CD6 belongs to the scavenger receptor cysteine-rich protein superfamil y (SRCRSF), which includes a large number of cell surface proteins, Th e extracellular region of CD6 is composed of three SRCR domains. The m embrane proximal SRCR domain of CD6 (CD6D3) specifically binds activat ed leukocyte cell adhesion molecule (ALCAM), a cell surface protein wh ich is a member of the immunoglobulin superfamily (IgSF), CD6-ligand i nteractions have been implicated in immune cell adhesion, T cell matur ation and the regulation of T cell activation, We tested 13 CD6D3 muta nt proteins for binding to ALCAM and a panel of conformationally sensi tive anti-CD6D3 monoclonal antibodies (mAbs), CD6D3 residues were clas sified according to their importance for structural integrity and liga nd binding, The results were analyzed in the light of SRCR domain sequ ence comparison, A number of residues critical for ligand binding or i mportant for structural integrity cluster in the C-terminal region of CD6D3 which is not conserved in other SRCR proteins.